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Background: Immune checkpoint inhibitors (ICIs) have been widely implemented in the treatment of solid tumors. Although epithelial ovarian carcinoma is considered as scarcely immunogenic, the presence of tumor-infiltrating T lymphocytes (TILs) in the ovarian tumor microenvironment (TME) could increase sensitivity to immune checkpoint inhibitors (ICIs). Combinations of ICIs with chemotherapy, anti-VEGF compounds and PARP inhibitors are under evaluation in ovarian cancer. Recently, a Phase II study evaluated the efficacy of Pembrolizumab in Combination with bevacizumab and oral cyclophosphamide in patients with recurrent platinum-sensitive, platinum-resistant, or refractory epithelial ovarian cancer.Methods: Herein, we present a retrospective study of all patients who received pembrolizumab in combination with bevacizumab and oral cyclophosphamide for recurrent platinum-resistant heavily pretreated ovarian cancer in the Oncology Unit of Alexandra University Hospital.Results: Median age at diagnosis was 54.5 years (SD; 8.9; range: 44–72). All patients were diagnosed with high-grade serous ovarian carcinoma (HGSC). Initial disease stage was FIGO IIIC (8/10; 80%), IIIB (1/10; 10%) and IIC (1/10; 10%)). Patients were heavily pretreated with a median of 6 (range: 4–9) prior lines of systemic therapy. All patients have experienced disease progression on first-line platinum-based chemotherapy and median PFS to first-line treatment was 20.1 months (95%CI; 11.4 – 28.7). Patients received a median of 4 cycles of pembrolizumab in combination with cyclophosphamide and bevacizumab (range 2-11). ORR was 20% (2/10) with two patients achieving partial response (PR) and two patients achieving stable disease (SD) while disease control rate (DCR) was 40% (4/10). Median PFS was 2.7 months (95%; 0.6 – 4.8) and 6-month PFS rate 20%. Conclusions: Though our data reflect a small population, we here demonstrate that the combination of pembrolizumab with bevacizumab and oral cyclophosphamide is an effective alternative in platinum-resistant recurrent ovarian carcinoma. This novel combination provides a promising alternative in heavily pretreated patients that have otherwise limited treatment options.

Undoubtedly, the development of COVID-19 vaccines displays a critical step towards ending this devastating pandemic, considering their protective benefits in the general population. Yet, data regarding their efficacy and safety in cancer patients are limited. Herein we provide the initial analysis of immune responses after the first dose of vaccination in 21 breast cancer patients receiving cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. The levels of neutralizing antibodies post vaccination were similar to the matched healthy controls, whereas no safety issues have been raised. Further exploration is needed to reduce the uncertainty of SARS-CoV-2 immunity among cancer patients under treatment.

Uterine serous carcinoma accounts for 3–10% of endometrial cancers, but it is the most lethal histopathological subtype. The molecular characterization of endometrial carcinomas has allowed novel therapeutic approaches for these patients. We undertook a retrospective analysis of patients with uterine serous carcinomas treated in our hospital within the last two decades to identify possible changes in their management. The patients and their characteristics were evenly distributed across the two decades. Treatment modalities did not change significantly throughout this period. After adjuvant treatment, patients’ median disease-free survival was 42.07 months (95% CI: 20.28–63.85), and it did not differ significantly between the two decades (p = 0.059). The median overall survival was 47.51 months (95% Cl: 32.18–62.83), and it significantly favored the first decade’s patients (p = 0.024). In patients with de novo metastatic or recurrent disease, median progression-free survival was 7.8 months (95% Cl: 5.81–9.93), whereas both the median progression-free survival and the median overall survival of these patients did not show any significant improvement during the examined time period. Overall, the results of our study explore the minor changes in respect of uterine serous carcinoma’s treatment over the last two decades, which are reflected in the survival outcomes of these patients and consequently underline the critical need for therapeutic advances in the near future.

Background: High grade serous ovarian carcinoma (HGSOC) is the most lethal type of epithelial ovarian cancer, with a prevalence of germline BRCA1/2 mutations as high as 20%. Our objective is to determine whether the location of mutations in the different domains of the BRCA1/2 genes affects the clinical outcome of HGSOC patients. Methods: A total of 51 women with BRCA1 or BRCA2 mutated ovarian cancer were identified. Progression-free survival (PFS) and overall survival (OS) were analyzed. Results: In our study cohort, 35 patients were carriers of germline mutations in BRCA1 and 16 in BRCA2. The median PFS time following completion of the primary therapy was 23.8 months (95% CI 20.1–27.5) and the median OS was 92.9 months (95% CI 69.8–116.1) in all BRCA carriers. After multivariate analysis, no significant association among the location or type of BRCA1/2 mutation with PFS or OS was identified. Notably, significant differences in PFS between carriers of identical mutations in the same BRCA gene were detected. Conclusions: Among HGSOC patients, BRCA1/2 carriers with mutations in different locations of the genes show no significant difference in survival outcomes, in terms of PFS and OS, suggesting the potential effect of other genetic abnormalities and co-contributing risk factors.

Background Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is the recommended approach in patients with advanced epithelial ovarian cancer (EOC). However, most patients eventually relapse despite the initial high response rate to chemotherapy. Neutrophil-to-lymphocyte ratio is a well-known biomarker that reflects severe inflammation, critical illness, and mortality in various diseases. Chemotherapy response score (CRS) and neutrophil-to-lymphocyte ratio (NLR) have been identified as potential biomarkers of platinum resistance and disease prognosis. We retrospectively evaluated 132 patients with stage IIIc or IV ovarian/fallopian tube/primary peritoneal cancer who had received NACT followed by IDS from 01/01/2003 to 31/12/2018. CRS was assessed on omental specimens collected from IDS according to ICCR guidelines. Results Median age was 64.57 years (SD: 9.72; range 39.2–87.1). Most ovarian tumors were serous epithelial (90.9%; 120/132). An elevated NLR (defined as > 3) was observed in 72% (95/132) of patients in contrast with 28% (37/132) of patients characterized by low NLR status. Median PFS (mPFS) and median overall survival (mOS) were 13.05 months (95% CI: 11.42–14.67)) and 34.69 months (95% CI: 23.26–46.12) respectively. In univariate analysis, CRS3 score was significantly associated with prolonged mPFS (CRS1/2: 12.79 months vs CRS3: 17.7 months; P = 0.008). CRS score was not associated with mOS (P = 0.876). High NLR was not significantly associated with mPFS (P = 0.128), however it was significantly associated with poor mOS (P = 0.012). In multivariate analysis, only performance of surgery maintained its statistical significance with both PFS (P = 0.001) and OS (P = 0.008). Conclusion NLR could serve as a useful predictor of OS but not PFS in ovarian cancer patients receiving NACT. In accordance with our previous study, CRS score at omentum was found to be associated with PFS but not OS in ovarian cancer patients treated with NACT and IDS., Research highlights Biomarkers that would predict response to neoadjuvant chemotherapy in advanced ovarian cancer patients are eagerly needed: • Neutrophil to Lymphocyte Ratio (NLR) is an indicator of systemic inflammatory response to the malignancy. • NLR was evaluated in 132 patients undergoing Neoadjuvant Chemotherapy for advanced ovarian cancer. • Elevated NLR was associated with worse prognosis. • No association between NLR and response to chemotherapy was noted.

Background Tumor protein 53 (TP53) gene mutations are identified in up to 37% of breast tumors especially in HER-2 positive and basal-like subtype. Previous studies have indicated TP53 mutations as a prognostic biomarker in breast cancer. However, most of these studies performed immunohistochemistry (IHC) for the detection of TP53 mutations. Aim The purpose of our study is to evaluate the role of TP53 somatic mutations detected via next-generation sequencing (NGS) as a potential prognostic marker in patients with breast cancer. Materials and methods 82 female patients with Stage I-III breast cancer underwent NGS in paraffin blocks and blood samples during the period 25/09/2019 through 25/05/2021. 23 cases of somatic TP53 mutations and 23 cases of healthy controls were matched on age at diagnosis, menopausal status, histological subtype, histological grade, ki67 expression and disease stage. Results Mean age at diagnosis was 52.35 (SD; 11.47) years. The somatic TP53 mutation NM_000546.5:c.824G>A p.(Cys275Tyr) was most frequently detected. Co-existence of PIK3CA mutation was a common finding in somatic TP53-mutant tumors (4/23; 17.4%). Disease-free survival was shorter in TP53-mutated cases (16.3 months vs. 62.9 months). TP53 pathogenic somatic mutations were associated with a 8-fold risk of recurrence in the univariate Cox regression analysis (OR = 8.530, 95% CI: 1.81-40.117; p = 0.007). Conclusions Our case-control study suggests that TP53 somatic mutations detected by next-generation sequencing (NGS) are associated with an adverse prognosis in breast cancer.

Cardiovascular disease is the leading cause of death worldwide. Given the increased availability of radiopharmaceuticals, improved positron emission tomography (PET) camera systems and proven higher diagnostic accuracy, PET is increasingly utilized in the management of various cardiovascular diseases. PET has high temporal and spatial resolution, when compared to Single Photon Emission Computed Tomography. In clinical practice, hybrid imaging with sequential PET and Computed Tomography acquisitions (PET/CT) or concurrent PET and Magnetic Resonance Imaging are standard. This article will review applications of cardiovascular PET/CT including myocardial perfusion, viability, cardiac sarcoidosis/inflammation, and infection.

Background Obesity and high body mass index (BMI) are associated with increased incidence of multiple myeloma (MM). MM usually evolves from a precursor asymptomatic disease, namely monoclonal gammopathy of undetermined significance (MGUS). MGUS progresses to MM at a 1% annual rate; however, risk factors predisposing to MGUS are not completely understood. We conducted a systematic review to assess the relationship between obesity and high BMI with MGUS prevalence and progression to MM. To our knowledge, this is the first systematic review evaluating the role of obesity in MGUS. Patients and Methods We searched the Medline database and ClinicalTrials.gov for studies investigating BMI and obesity association with MGUS incidence and progression. The algorithm consisted of a predefined combination of the words “obesity,” “obese,” “body mass index,” “overweight,” “diet,” “nutrition,” “food,” “dietary,” “adiponectin,” “monoclonal gammopathy,” and “MGUS”. Results Overall, 12 articles were retrieved, including 11 eligible articles and 1 clinical trial. More than 57,068 patients were evaluated in this systematic review. Discrepancies between the identified studies were noted. Multiple studies support the notion that obesity or high BMI are positively linked to MGUS prevalence and transition to MM. In contrast, other studies revealed no such association. Visceral adipose tissue metabolic activity and decreased adiponectin concentrations were identified as biomarkers of MGUS progression to MM. Conclusion Obesity and increased BMI seem to be implicated both in MGUS development and progression to MM. Further studies should be designed to confirm this hypothesis.

OBJECTIVE Several studies have evaluated the differences in duration of latency and clinical outcomes between singleton and twin pregnancies after preterm premature rupture of membranes (PPROM); however, these data are limited to single-institution analyses and based on small sample sizes. The aim of this study was to assess differences in latency and clinical outcomes in singletons versus twin gestations affected by PPROM in a large, diverse cohort of women. STUDY DESIGN This is a secondary analysis of a multicenter trial of magnesium for neuroprotection in women at high risk of preterm birth. Our study included women with PPROM ≥ 24 weeks with singleton and twin gestations. We compared singleton versus twin gestation and our primary outcome was duration of latency after PPROM. Secondary outcomes included selected perinatal and neonatal outcomes including long-term neurodevelopmental outcomes. We fit a linear regression model to assess independent risk factors for latency duration. RESULTS Our study included 1,753 women, 1,602 singleton gestations (91%) and 151 twin gestations (9%). The median latency period was significantly shorter in twins (4 [interquartile range, IQR: 1-10] vs. 7 [IQR: 3-16] days, p

Objective This study was aimed to review 4 weeks of universal novel coronavirus disease 2019 (COVID-19) screening among delivery hospitalizations, at two hospitals in March and April 2020 in New York City, to compare outcomes between patients based on COVID-19 status and to determine whether demographic risk factors and symptoms predicted screening positive for COVID-19. Study Design This retrospective cohort study evaluated all patients admitted for delivery from March 22 to April 18, 2020, at two New York City hospitals. Obstetrical and neonatal outcomes were collected. The relationship between COVID-19 and demographic, clinical, and maternal and neonatal outcome data was evaluated. Demographic data included the number of COVID-19 cases ascertained by ZIP code of residence. Adjusted logistic regression models were performed to determine predictability of demographic risk factors for COVID-19. Results Of 454 women delivered, 79 (17%) had COVID-19. Of those, 27.9% (n = 22) had symptoms such as cough (13.9%), fever (10.1%), chest pain (5.1%), and myalgia (5.1%). While women with COVID-19 were more likely to live in the ZIP codes quartile with the most cases (47 vs. 41%) and less likely to live in the ZIP code quartile with the fewest cases (6 vs. 14%), these comparisons were not statistically significant (p = 0.18). Women with COVID-19 were less likely to have a vaginal delivery (55.2 vs. 51.9%, p = 0.04) and had a significantly longer postpartum length of stay with cesarean (2.00 vs. 2.67days, p Conclusion COVID-19 symptoms were present in a minority of COVID-19-positive women admitted for delivery. Significant differences in obstetrical outcomes were found. While demographic risk factors demonstrated acceptable discrimination, risk prediction does not capture a significant portion of COVID-19-positive patients. Key Points

Treatment of elderly patients with neoplasia is challenging. Age is a known prognostic factor in ovarian cancer but the optimal treatment of elderly patients has not been determined. We undertook a retrospective analysis to determine clinical practice in advanced-stage ovarian cancer patients older than 70 years of age. Methods: Medical records of women with high-grade serous ovarian cancer, stage III and IV were retrospectively analyzed. Results: A total of 735 patients were identified with a median age of 61.5 years. 22.4% among them were older than 70 years of age at diagnosis. First-line Progression-Free Survival (PFS) and Overall Survival (OS) were significantly worse in elderly patients in comparison to the younger ones [mPFS 11.3 months vs., 14.8 months, (p &lt, 0.001) and mOS 30.2 months vs. 45.6 months (p &lt, 0.001)]. However, elderly patients were characterized by worse ECOG-Performance Status and they were more frequently treated with Neoadjuvant Chemotherapy followed by Interval Debulking Surgery, while often they were more frequently denied debulking surgery compared to patients under 70 years of age. Moreover, elderly patients received more frequently monotherapy with platinum as frontline treatment. In contrast, there was no significant difference in the outcome of the debulking surgery in comparison to the younger patients or the frequency that gBRCA test was performed. Age over 70 years did not retain its significance for either Progression-Free Survival or Overall Survival when adjusted for all other reported prognostic factors. Conclusion: Elderly ovarian cancer patients have a worse prognosis. Comprehensive geriatric assessment should be performed for the optimal treatment of these patients.

Bromodomain and extra-terminal (BET) proteins are epigenetic readers that bind to acetylated lysines of histones and regulate gene transcription. BET protein family members mediate the expression of various oncogenic drivers in ovarian cancer, such as the MYC and Neuregulin 1 (NRG1) genes. BRD4, the most thoroughly studied member of the BET family, is amplified in a significant subset of high-grade serous carcinomas (HGSC) of the ovary. It has been reported that BET inhibitors can attenuate the proliferation and dissemination of ovarian cancer cells by inhibiting oncogenic pathways, such as the FOXM1 and JAK/STAT pathways. BET inhibition can re-sensitize resistant ovarian cancer cells to already approved anticancer agents, including cisplatin and PARP inhibitors. This synergism was also confirmed in vivo in animal models. These and other preclinical results provide a promising basis for the application of BET inhibitors in ovarian cancer treatment. Currently, Phase I/II clinical trials explore the safety and efficacy profiles of BET inhibitors in various solid tumors, including ovarian tumors. Here, we review current knowledge on the molecular effects and preclinical activities of BET inhibitors in ovarian tumors. BET proteins have emerged as new druggable targets for ovarian cancer. BET inhibitors may enhance antitumor activity when co-administered with conventional treatment regimens. Results from ongoing Phase I/II studies are anticipated to confirm this notion.

Bromodomain and extraterminal domain (BET) proteins are epigenetic molecules that regulate the expression of multiple genes involved in carcinogenesis. Breast cancer is an heterogenous disease emerging from aberrant gene expression and epigenetic alteration patterns. Amplification or overexpression of BET proteins has been identified in breast tumors highlighting their clinical significance. Development of BET inhibitors that disrupt BET protein binding to acetylated lysine residues of chromatin and suppress transcription of various oncogenes has shown promising results in breast cancer cells and xenograft models. Currently, Phase I/II clinical trials explore safety and efficacy of BET inhibitors in solid tumors and breast cancer. Treatment-emergent toxicities have been reported, including thrombocytopenia and gastrointestinal disorders. Preliminary results demonstrated greater response rates to BET inhibitors in combination with already approved anticancer agents. Consistently, BET inhibition sensitized breast tumors to chemotherapy drugs, hormone therapy and PI3K inhibitors in vitro. This article aims to review all existing preclinical and clinical evidence regarding BET inhibitors in breast cancer., Highlights • BET proteins are epigenetic readers that regulate transcription of multiple cancer-associated genes. • BET inhibitors attenuate BET protein association to chromatin suppressing oncogene pathways. • Preclinical studies have shown promising efficacy of BET inhibitors in breast cancer murine xenografts and cell lines. • BET inhibitors provided an additive effect to widely used anticancer agents, including chemotherapy drugs, hormone therapy and tyrosine kinase inhibitors. • Ongoing Phase I/II trials revealed a potent BETi antitumor efficacy and safety limitations due to hematologic and gastrointestinal toxicity.

OBJECTIVE: To describe risk of Clostridium difficile infection associated with clindamycin and acute kidney injury associated with gentamicin during delivery hospitalizations. METHODS: Women admitted for delivery from January 2006 to March 2015 were analyzed using an inpatient administrative database. Primary outcomes were C. difficile infection and acute kidney injury. Clostridium difficile infection was compared between women receiving clindamycin (with or without other antibiotics) and women receiving antibiotics other than clindamycin. Acute kidney injury was compared between women receiving gentamicin (with or without other antibiotics), women receiving antibiotics other than gentamicin, and women receiving no antibiotics. Unadjusted and adjusted log linear models analyzing the role of patient demographics, mode of delivery, and hospital-level characteristics were created evaluating risk for C. difficile infection and acute kidney injury with risk ratios (RR) and adjusted risk ratios with 95% confidence intervals (CI) as measures of association. A sensitivity analysis for gentamicin and acute kidney injury was performed restricted to women with preeclampsia. RESULTS: Of 5,657,523 women admitted for delivery hospitalization, 266,402 (4.7%) received clindamycin and 165,726 (2.9%) received gentamicin. Clostridium difficile infection was diagnosed in 0.04% of women receiving clindamycin. Compared to women receiving other antibiotics, clindamycin was associated with a nearly three-fold increased risk of C. difficile infection (RR 2.93, 95% CI 2.36, 3.65). Acute kidney injury was diagnosed in 0.24% of women receiving gentamicin. Gentamicin was associated with a three-fold risk of acute kidney injury (RR 3.01, 95% CI 2.71, 3.34) compared to women receiving other antibiotics, while receipt of no antibiotics was associated with significantly lower risk (RR 0.18, 95% CI 0.15, 0.20). In adjusted analyses, these associations retained significance. Significantly increased risk for acute kidney injury was noted with women with preeclampsia receiving gentamicin (RR 2.04, 95% CI 1.64, 2.53). CONCLUSION: Receipt of clindamycin was associated with significantly increased likelihood for C. difficile infection and receipt of gentamicin with significantly increased likelihood of acute kidney injury, although the absolute risk for these complications was low.

Objective Trends in use of antibiotics during delivery hospitalizations complicated by (1) 3rd/4th degree vaginal lacerations, (2) manual placenta extraction, and (3) uterine tamponade are not well characterized. The objective of this study was to analyze trends in antibiotic use during vaginal delivery hospitalizations complicated by these three clinical scenarios. Study Design An administrative inpatient database was used to perform a serial cross-sectional analysis of antibiotic administration during delivery hospitalizations in the United States from January 2006 to March 2015. The primary outcome was receipt of antibiotics during vaginal delivery hospitalizations complicated by (1) 3rd and 4th degree vaginal lacerations, (2) manual placenta extraction, and (3) uterine tamponade. Patients with other indications for antibiotics were excluded. The Cochran–Armitage test was used to assess trends. Adjusted log linear regression analyses including demographic, hospital, and obstetric factors were performed to analyze factors associated with antibiotic receipt for each of these three clinical scenarios in both primary and sensitivity analyses. Results From 2006 to 2015 the rate of antibiotic administration during delivery hospitalizations decreased from 43.1% in 2006 to 25.5% for 3rd and 4th degree lacerations and from 59.6% to 49.2% for manual extraction (p Conclusion Antibiotics are not used consistently during vaginal deliveries complicated by 3rd/4th degree lacerations, manual placenta extraction, and uterine tamponade. These findings support that a significant opportunity exists for comparative effectiveness research to assist in characterizing best practices.

Recently, immunotherapy has shown promising results in solid tumors. To the best of our knowledge, this is the first systematic review of published literature synthesizing all the available data and evaluating both the efficacy and safety of pembrolizumab in endometrial cancer. The present study was performed in accordance with the PRISMA guidelines. Eligible articles were identified by searching the MEDLINE and ClinicalTrials.gov databases, using a predefined combination of the terms 'endometrial cancer' and 'pembrolizumab'. Overall, nine articles incorporating data from 712 patients were eligible. Pembrolizumab was demonstrated to be an effective and safe therapeutic option for the management of advanced/metastatic endometrial cancer. Results of ongoing trials evaluating either pembrolizumab alone or in combination with other antineoplastic regimens are expected to confirm its efficacy in this setting of patients. Pembrolizumab appears to be both durable and robust in endometrial cancer. However, there is an emerging need for novel predictive biomarkers to guide clinical practice.

Background Immune checkpoint inhibitors have been widely implemented in current clinical practice. Although cancer occurs in ∼1 out of 1000 pregnancies, treatment remains challenging. Until now, limited data exist regarding immunotherapy administration during pregnancy. This systemic review aims to synthesize all available data from immunotherapy administration in pregnant women and evaluate the efficacy and safety of immunotherapy during pregnancy. Patients and methods Eligible studies were identified by a search of the PubMed Medline database and Food and Drug Administration Adverse Events Reporting System Public Dashboard for the period 1 January 2000 to 1 April 2021; the algorithm consisted of a predefined combination of the words ‘immunotherapy’, ‘cancer’ and ‘pregnancy’. PRISMA guidelines were applied in this study. Results Overall, seven articles (seven pregnancies, nine neonates) were retrieved. The mean duration of immunotherapy administration was 9.8 weeks [standard deviation (SD): 11.27; median: 7.0; range: 1-32]. In all cases specified, melanoma was the malignancy reported. The mean gestational age at delivery was 30.4 weeks (SD: 5.03; median: 32.0; range: 24-38), whereas the mean weight of neonates at delivery was 1267 g (SD: 412.0; median: 1400; range: 590-1701). Only one neonate was born term at 38 weeks of pregnancy (11.1%; 1/9). Complications during pregnancy were observed in 71.4% of cases: intrauterine growth restriction (three cases), HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count) (one case), placental insufficiency (one case) and low fetal heart rate (one case). The mean progression-free survival and overall survival were 16.0 and 25.2 months, respectively. Conclusion The administration of immune checkpoint inhibitors during pregnancy is associated with increased incidence of pregnancy complications, prematurity and low birth weight. The administration of these regimens is not recommended during gestation. Whenever applied, close monitoring of the mother and the fetus is required., Highlights • About 1 in 1000 pregnant women are diagnosed with cancer. • Anti-PD-1 agents are categorized as pregnancy category D by the FDA, whereas ipilimumab is category C. • We report for the first time all cases of exposure to immunotherapy during pregnancy. • In most cases a premature neonate was born (88.9%) whereas in 71.4% of cases complications during pregnancy were reported. • For now, the administration of immune checkpoint inhibitors during pregnancy should be discouraged.

The precise etiology of multiple myeloma remains elusive, but both genetic and environmental factors have been suggested to contribute to disease risk. Several occupational categories and toxic agents have been implicated as potentially causative, yet findings from the literature are inconsistent. The aim of this review was to summarize and critically comment on the accumulated epidemiological evidence, across published meta-analyses, about the association between occupational exposure and risk of multiple myeloma. Overall, results from eleven meta-epidemiological studies underscore a significantly increased risk for firefighters, hairdressers, and employees exposed to engine exhaust, whereas farming and methylene chloride exposure have been non-significantly correlated with the disease. Further epidemiological studies are of utmost importance whilst emphasis should be placed on occupational hazard surveillance, as such studies will obtain a more accurate picture of disease occurrence in working populations, and will enable both the implementation of preventive actions and the evaluation of their effectiveness.

This study aimed to evaluate maternal and neonatal outcomes by method of cervical ripening for labor induction among low-risk nulliparous individuals. This is a secondary analysis of a multicenter randomized trial of labor induction at 39 weeks versus expectant management in low-risk nulliparous participants. Participants undergoing cervical ripening for labor induction in either group were included. Participants were excluded for preripening membrane rupture, abruption, chorioamnionitis, fetal demise, or cervical dilation ≥3.5 cm. Cervical ripening was defined by the initial method used: prostaglandin only (PGE; referent), Foley with concurrent prostaglandin (Foley-PGE), Foley only (Foley), and Foley with concurrent oxytocin (Foley-oxytocin). Coprimary outcomes were adverse maternal and neonatal composites. Secondary outcomes included cesarean delivery and length of labor and delivery (LD) stay. Multivariable analysis was used to adjust for patient characteristics. Of 6,106 participants included in the trial, 2,376 (38.9%) met criteria for this analysis. Of these, 1,247 (52.4%) had cervical ripening with PGE, 290 (12.2%) had Foley-PGE, 385 (16.2%) had Foley, and 454 (19.1%) had Foley-oxytocin. The maternal composite outcome was similar among participants who received Foley-PGE (24.1%, adjusted relative risk [aRR] = 1.21, 95% confidence interval [CI]: 0.96-1.52), Foley (21.3%, aRR = 1.16, 95% CI: 0.92-1.45), or Foley-oxytocin (19.4%, aRR = 1.04, 95% CI: 0.83-1.29), compared with PGE (19.7%). The neonatal composite outcome was less frequent in participants who received the Foley-PGE (2.4%, aRR = 0.35, 95% CI: 0.16-0.75) or Foley (3.6%, aRR = 0.51, 95% CI: 0.29-0.89) but did not reach statistical significance for participants who received Foley-oxytocin (4.6%, aRR = 0.63, 95% CI: 0.40-1.01) compared with PGE only (6.8%). Participants who received Foley-PGE or Foley-oxytocin had a shorter LD stay (adjusted mean difference = -1.97 hours, 95% CI: -3.45 to -0.49 and -5.92 hours, 95% CI: -7.07 to -4.77, respectively), compared with PGE. In term low-risk nulliparous participants, Foley alone or concurrent with PGE is associated with a lower risk of adverse neonatal outcomes than with PGE alone. Length of LD stay was the shortest with concurrent Foley-oxytocin.· Adverse maternal outcomes are similar among different methods of cervical ripening in low-risk women.. · Adverse neonatal outcomes are less frequent with use of Foley alone or in combination with PGE.. · The use of Foley alone, or in combination with other agents, appears to be beneficial..

Background Oral neural tumors (ONTs) are rare lesions and represent reactive or neoplastic proliferations of nerve sheath cells. The purpose of the present study is to report the clinical, demographic and histopathologic features of 157 ONTs diagnosed in a single Oral Pathology Department and review the pertinent literature. Material and methods 157 cases of ONTs diagnosed during a 44-year period were retrospectively collected and the diagnosis was reconfirmed by studying representative haematoxylin and eosin stained tissue sections. The patients' gender and age, as well as the main clinical features of the lesions, were retrieved from the biopsy submission forms. Results The 157 ONTs represented approximately 0.4% of 35,590 biopsies accessioned during the study period. They affected 71 male and 86 female patients with a mean age of 38.4±18.8 years. They mainly appeared as asymptomatic nodules of normal or white colour on the tongue, lip mucosa and hard palate. The most common ONT was granular cell tumour (38.9%) followed by neurofibroma (19.7%), schwannoma (15.9%), traumatic neuroma (15.9%), palisaded encapsulated neuroma (8.3%) and nerve sheath myxoma (1.3%). Conclusions This study confirmed the rarity of ONTs. Their clinical characteristics mimic other oral lesions; thus, microscopic examination is the only mean to arrive at a definitive diagnosis. Key words:Oral neural tumors; oral neural neoplasms; neurofibroma; oral neurofibroma; schwannoma; oral schwannoma; neurilemmoma; oral neurilemmoma; granular cell tumor; oral granular cell tumor; traumatic neuroma; oral traumatic neuroma; palisaded encapsulated neuroma; oral palisaded encapsulated neuroma.

The aim of the present study is to report the demographic and clinical characteristics of all jaw cysts diagnosed in a single Oral Pathology Department. 5294 cases of jaw cysts diagnosed during a 38-year period were retrospectively collected and classified according to the latest classification of Head and Neck Tumors of the World Health Organization. The patients' gender and age, as well as the main clinical features of the cysts were retrieved from biopsy report forms. Jaw cysts were more common in male patients, with a male to female ratio of 1.6:1. Most patients were in the 4th-6th decade of life, with a mean age of 42.3 ± 16.1 years. There was no jaw predilection and the majority of lesions were more commonly encountered in the anterior region of the maxilla, followed by the molar region of the mandible. The most common jaw cyst was radicular cyst followed by dentigerous cyst, residual cyst and odontogenic keratocyst. The majority of jaw cysts are of inflammatory origin and represent a sequale of pulp necrosis. However, other type of jaw cysts may also be found.

Postpartum hemorrhage is the leading cause of maternal morbidity and mortality worldwide. The majority of maternal deaths associated with hemorrhage could be preventable. The accurate assessment of blood loss, identification of risk factors and timely recognition of postpartum hemorrhage remain major challenges in obstetrics. It is important to review available modalities for estimation and quantification of peripartum blood loss, the value of risk assessment tools as well as the challenges in early recognition of clinical signs and symptoms of postpartum hemorrhage.

Data regarding the safety and efficacy of COVID-10 vaccines among cancer patients are lacking. Factors such as age, underlying disease and antineoplastic treatment confer negatively to the immune response due to vaccination. The degree of immunosuppression though may be lessen by targeted treatments like the androgen receptor-targeted agents (ARTA) that are commonly used in patients with metastatic prostate cancer. Herein, we report our data on 25 patients with prostate cancer under treatment with ARTA who were vaccinated for COVID-19. Our data suggest that these patients develop neutralizing antibodies against SARS-CoV-2 similarly to healthy volunteers. No safety issues were noted.

Background: Breast cancer remains the most common cancer in women and a leading cause of death. Elderly people have a higher incidence of breast cancer since it increases with age. Furthermore, the extended life expectancy and advances in imaging techniques have led to an increased number of cases. Guidelines concerning the management of this specific age group are rare, mainly due to underrepresentation of seniors in clinical trials. Moreover, increased frailty, comorbidities, and a poor performance status make it complex to determine the best therapeutic approach. Summary: In this review, we attempt to summarize the current literature and aim to provide specific approaches and recommendations for prompt diagnosis, treatment, and management of breast cancer in the elderly. Key Messages: The establishment of applicable protocols is imperative and efforts are being made in this direction. A careful geriatric assessment and adequate consultation should be the standard of care and patient’s preferences should always be considered.

Introduction Pregnancy is characterized by increased appetitive drive beginning early in gestation, yet the central mechanisms underlying this adaptation are poorly understood in humans. To elucidate central mechanisms underlying appetite regulation in early pregnancy, we examine plasma and cerebrospinal fluid (CSF) leptin and Agouti-related peptide (AgRP) as well as CSF proopiomelanocortin (POMC) as surrogates for brain melanocortin activity. Methods Plasma leptin, soluble leptin receptor, AgRP, and CSF leptin, POMC, and AgRP were collected from pregnant women before cerclage placement (16.6 ± 1.1 weeks; N = 24), scheduled cesarean section (39.2 ± 0.2 weeks; N = 24), and from nonpregnant controls (N = 24), matched for age and body mass index. Results Plasma leptin was 1.5 times higher in pregnancy vs controls (P = 0.01), but CSF leptin did not differ. CSF/plasma leptin percentage was lower in early pregnancy vs controls (0.8 ± 0.1 vs 1.7 ± 0.2; P Conclusions Pregnancy-specific adaptions in the central regulation of energy balance occur early in human gestation and are consistent with decreased leptin transport into brain and resistance to the effects of leptin on target melanocortin neuropeptides.

Background Over than one third (28–58%) of pregnancy-associated breast cancer (PABC) cases are characterized by positive epidermal growth factor receptor 2-positive (HER2) expression. Trastuzumab anti-HER2 monoclonal antibody is still the benchmark treatment of HER2-positive breast tumors. However, FDA has categorized Trastuzumab as a category D drug for pregnant patients with breast cancer. This systemic review aims to synthesize all currently available data of trastuzumab administration during pregnancy and provide an updated view of the effect of trastuzumab on fetal and maternal outcome. Methods Eligible articles were identified by a search of MEDLINE bibliographic database and ClinicalTrials.gov for the period up to 01/09/2020; The algorithm consisted of a predefined combination of the words “breast”, “cancer”, “trastuzumab” and “pregnancy”. This study was performed in accordance with the PRISMA guidelines. Results A total of 28 eligible studies were identified (30 patients, 32 fetuses). In more than half of cases, trastuzumab was administered in the metastatic setting. The mean duration of trastuzumab administration during gestation was 15.7 weeks (SD: 10.8; median: 17.5; range: 1–32). Oligohydramnios or anhydramnios was the most common (58.1%) adverse event reported in all cases. There was a statistically significant decrease in oligohydramnios/anhydramnios incidence in patients receiving trastuzumab only during the first trimester (P = 0.026, Fisher’s exact test). In 43.3% of cases a completely healthy neonate was born. 41.7% of fetuses exposed to trastuzumab during the second and/or third trimester were born completely healthy versus 75.0% of fetuses exposed exclusively in the first trimester. All mothers were alive at a median follow-up of 47.0 months (ranging between 9 and 100 months). Of note, there were three cases (10%) of cardiotoxicity and decreased ejection fraction during pregnancy. Conclusions Overall, treatment with trastuzumab should be postponed until after delivery, otherwise pregnancy should be closely monitored.

Background Individuals with sickle cell disease (SCD) are at risk for painful crises and long-term cardiopulmonary morbidity. Echocardiogram is recommended if signs or symptoms of cardiopulmonary disease develop in previously asymptomatic patients, or worsen in those with known disease. Second-generation echocardiogram contrast agents (ECAs) improve the diagnostic capacity of echocardiogram; however, these agents have risks in SCD populations that have yet to be investigated. Case summary We report a case series of two patients who experienced vaso-occlusive crises following administration of the ECA, Definity. Both patients were referred for echocardiogram from our institution’s sickle cell clinic because of concern for SCD-related cardiopulmonary complications. Both patients were in their usual state of health at the time of their exams. The first patient experienced acute back and hip pain minutes after receiving Definity and was diagnosed with acute vaso-occlusive crisis requiring admission for 6 days for pain management. The second patient developed dyspnoea and chest pain within 90 min of her echocardiogram. She was diagnosed with acute chest syndrome and admitted for further management. Her hospitalization was complicated by hyper-haemolysis and multiple organ failure syndrome. After 13 days, she was discharged home. Discussion The safety profile of ECAs has not been fully evaluated and warrants further study in individuals with SCD. Proposed mechanisms for our observations include the release of pro-inflammatory metabolites from Definity contrast agent’s shell and ultrasound-induced haemolysis secondary to ECA administration. Alternative imaging modalities and proper precautions should be considered when evaluating cardiopulmonary function in this patient population.

Simple Summary Aromatase inhibitor-induced musculoskeletal symptoms (AIMSS) occurs in up 50% of postmenopausal patients and is the reason for treatment discontinuation in 25% of patients with breast cancer. CDK4/6 inhibitors have been established in the treatment of hormone receptor-positive (HR) breast cancer. We aimed to assess the effect of treatment with CDK4/6 inhibitors on AIMSS. Arthralgia rate was lower in patients receiving aromatase inhibitors (AIs) in combination with CDK4/6 inhibitors (5.8–33.3%) compared with monotherapy with AIs (1–47%). Myalgias, back pain and bone pain also tended to be reduced in patients treated with CDK4/6 inhibitors. CDK4/6 inhibitors may alleviate musculoskeletal pain caused by AIs, although further studies are warranted. Abstract Background: Treatment with aromatase inhibitors (AIs) is fundamental in women with hormone receptor-positive breast cancer in the adjuvant as well as the metastatic setting. Even though it is considered to be a well-tolerated therapy, aromatase inhibitor-associated musculoskeletal syndrome (AIMSS) is the most common adverse event encountered by breast cancer patients. CDK4/6 inhibitors have emerged as a new treatment strategy in metastatic hormone receptor-positive breast cancer. However, the impact of CDK4/6 inhibitors on musculoskeletal symptoms caused by AIs is not well-defined. Objectives: This systematic review aims to identify the frequency of joint symptoms induced by treatment with AIs and CDK4/6 inhibitors in the metastatic setting. Search strategy: Eligible articles were identified by a search of existing literature for the period 2005/01/01–2021/01/01; The algorithm consisted of a predefined combination of the following keywords “breast”, “cancer”, “aromatase inhibitors”, “CDK4/6”, “phase III”. Selection criteria: This study was performed in accordance with PRISMA guidelines. All randomized controlled Phase III trials (RCTs) evaluating the administration of third-generation aromatase inhibitors (AIs) and CDK4/6 inhibitors in postmenopausal women in the metastatic setting were considered eligible for this review. Data collection: Overall, 16 randomized control trials (RCTs) were retrieved, of which nine studies explored the administration of AIs in the metastatic setting and seven studies investigated the combination of CDK4/6 inhibitors and AIs. Arthralgia was reported in 1–47% of patients treated with AIs and 5.8–33.3% of patients treated with CDK4/6 inhibitors. Myalgias occurred in 2–23.7% of patients receiving AIs compared with 4.8–11.9% of patients treated with CDK4/6 inhibitors. The incidence of back pain was 7–32.9% vs. 2.9–8.5% in postmenopausal women with metastatic disease treated with AIs and CDK4/6 inhibitors, respectively. Bone pain was reported in 7–32.9% of postmenopausal women treated with AIs and 2.9–8.5% of women treated with CDK4/6 inhibitors. Conclusions: AI treatment-induced musculoskeletal syndrome is an adverse event affecting over one-third (20–47%) of postmenopausal patients treated with AIs that often leads to treatment discontinuation. Data from RCTs provide evidence that the incidence of musculoskeletal symptoms is relatively decreased upon CDK4/6 inhibitor administration. CDK4/6 inhibitors may provide a protective role against AIMSS development.

IMPORTANCE: Limited data on vertical and perinatal transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and health outcomes of neonates born to mothers with symptomatic or asymptomatic coronavirus disease 2019 (COVID-19) are available. Studies are needed to inform evidence-based infection prevention and control (IP&C) policies. OBJECTIVE: To describe the outcomes of neonates born to mothers with perinatal SARS-CoV-2 infection and the IP&C practices associated with these outcomes. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort analysis reviewed the medical records for maternal and newborn data for all 101 neonates born to 100 mothers positive for or with suspected SARS-CoV-2 infection from March 13 to April 24, 2020. Testing for SARS-CoV-2 was performed using Cobas (Roche Diagnostics) or Xpert Xpress (Cepheid) assays. Newborns were admitted to well-baby nurseries (WBNs) (82 infants) and neonatal intensive care units (NICUs) (19 infants) in 2 affiliate hospitals at a large academic medical center in New York, New York. Newborns from the WBNs roomed-in with their mothers, who were required to wear masks. Direct breastfeeding after appropriate hygiene was encouraged. EXPOSURES: Perinatal exposure to maternal asymptomatic/mild vs severe/critical COVID-19. MAIN OUTCOMES AND MEASURES: The primary outcome was newborn SARS-CoV-2 testing results. Maternal COVID-19 status was classified as asymptomatic/mildly symptomatic vs severe/critical. Newborn characteristics and clinical courses were compared across maternal COVID-19 severity. RESULTS: In total, 141 tests were obtained from 101 newborns (54 girls [53.5%]) on 0 to 25 days of life (DOL-0 to DOL-25) (median, DOL-1; interquartile range [IQR], DOL-1 to DOL-3). Two newborns had indeterminate test results, indicative of low viral load (2.0%; 95% CI, 0.2%-7.0%); 1 newborn never underwent retesting but remained well on follow-up, and the other had negative results on retesting. Maternal severe/critical COVID-19 was associated with newborns born approximately 1 week earlier (median gestational age, 37.9 [IQR, 37.1-38.4] vs 39.1 [IQR, 38.3-40.2] weeks; P = .02) and at increased risk of requiring phototherapy (3 of 10 [30.0%] vs 6 of 91 [7.0%]; P = .04) compared with newborns of mothers with asymptomatic/mild COVID-19. Fifty-five newborns were followed up in a new COVID-19 Newborn Follow-up Clinic at DOL-3 to DOL-10 and remained well. Twenty of these newborns plus 3 newborns followed up elsewhere had 32 nonroutine encounters documented at DOL-3 to DOL-25, and none had evidence of SARS-CoV-2 infection, including 6 with negative retesting results. CONCLUSIONS AND RELEVANCE: No clinical evidence of vertical transmission was identified in 101 newborns of mothers positive for or with suspected SARS-CoV-2 infection, despite most newborns rooming-in and direct breastfeeding practices.

ERCC1 is a key regulator of nucleotide excision repair (NER) pathway that repairs bulky DNA adducts, including intrastrand DNA adducts and interstrand crosslinks (ICLs). Overexpression of ERCC1 has been linked to increased DNA repair capacity and platinum resistance in solid tumors. Multiple single nucleotide polymorphisms (SNPs) have been detected in ERCC1 gene that may affect ERCC1 protein expression. Platinum-based treatment remains the cornerstone of urothelial cancer treatment. Given the expanding application of neoadjuvant and adjuvant chemotherapy in locally advanced bladder cancer, there is an emerging need for biomarkers that could distinguish potential responders to cisplatin treatment. Extensive research has been done regarding the prognostic and predictive role of ERCC1 gene expression and polymorphisms in bladder cancer. Moreover, novel compounds have been recently developed to target ERCC1 protein function in order to maximize sensitivity to cisplatin. We aim to review all the existing literature regarding the role of the ERCC1 gene in bladder cancer and address future perspectives for its clinical application.

Novel chemotherapeutic agents have marked a new era in oncology during the past decade, prolonging significantly the overall survival of breast cancer patients. Nevertheless, contemporary antineoplastic treatments can frequently cause adverse cardiovascular side effects. Common manifestations of chemotherapy-induced cardiotoxicity include cardiomyopathy, ischemia, conduction disturbances, hypertension and thromboembolic events, while the type of the treatment regimen administered crucially determines clinical outcome. The aim of this literature review is to analyze the incidence and the underlying mechanisms of cardiovascular toxicity caused by agents approved for breast cancer, as well as to describe ways of monitoring and treating the cardiotoxic effects in breast cancer patients. Moreover, our work intends to provide an easy-to-grasp synopsis of recent and clinically meaningful advances in the field.

T-cell lymphomas are infrequently encountered in the head and neck area, with the most common subtype being Extranodal NK/T cell lymphoma, nasal type (ENKTL-NT). ENKTL-NT shows a predilection for midline facial structures presenting with ulcerative destructive lesions, whereas palatal involvement is one of the most prominent signs from the oral cavity. Herein, we describe a case of a 76-year-old Greek man with nasal obstruction and an extensive painful necrotic ulcer with ragged borders on the left distal portion of the soft palate and palatine tonsil of 4-months duration. After an initial non-diagnostic biopsy from the nasopharynx, a second incisional biopsy from the palatal lesions was performed. Histopathology was suggestive of an angiocentric lymphoproliferative neoplasm and immunohistochemical examination and in situ hybridization for EBV RNA led to a final diagnosis of ENKTL-NT. The patient was placed under combined chemotherapy and radiotherapy and no recurrence has been noted. Additionally, a retrospective review of the cases in the English literature with an established diagnosis of ENTKL-NT between 2000 and 2019, based on the latest WHO classification of Head and Neck tumors, is performed.

Novel coronavirus disease 2019 is rapidly spreading throughout the New York metropolitan area since its first reported case on March 1, 2020. The state is now the epicenter of coronavirus disease 2019 outbreak in the United States, with 84,735 cases reported as of April 2, 2020. We previously presented an early case series with 7 coronavirus disease 2019–positive pregnant patients, 2 of whom were diagnosed with coronavirus disease 2019 after an initial asymptomatic presentation. We now describe a series of 43 test-positive cases of coronavirus disease 2019 presenting to an affiliated pair of New York City hospitals for more than 2 weeks, from March 13, 2020, to March 27, 2020. A total of 14 patients (32.6%) presented without any coronavirus disease 2019–associated viral symptoms and were identified after they developed symptoms during admission or after the implementation of universal testing for all obstetric admissions on March 22. Among them, 10 patients (71.4%) developed symptoms of coronavirus disease 2019 over the course of their delivery admission or early after postpartum discharge. Of the other 29 patients (67.4%) who presented with symptomatic coronavirus disease 2019, 3 women ultimately required antenatal admission for viral symptoms, and another patient re-presented with worsening respiratory status requiring oxygen supplementation 6 days postpartum after a successful labor induction. There were no confirmed cases of coronavirus disease 2019 detected in neonates upon initial testing on the first day of life. Based on coronavirus disease 2019 disease severity characteristics by Wu and McGoogan, 37 women (86%) exhibited mild disease, 4 (9.3%) severe disease, and 2 (4.7%) critical disease; these percentages are similar to those described in nonpregnant adults with coronavirus disease 2019 (about 80% mild, 15% severe, and 5% critical disease).

Objective Hemolysis, characterized by formation of free hemoglobin (Hb), occurs in patients undergoing cardiopulmonary bypass (CPB). However, there is no study of the dynamic changes in red blood cell (RBC)-derived exosomes (Exos) released during CPB, nor whether these particles mediate acute kidney injury (AKI). Methods This study is a comprehensive time–course analysis, at baseline, 30 minutes, to 24 hours post-crossclamp release (XCR) to determine (1) Exos Hb content; (2) free Hb/heme, haptoglobin, hemopexin; and (3) urinary markers of AKI over the same time period. In addition, we developed a model system in Sprague–Dawley rats to test for AKI after intravenous injection of Exos Hb released during CPB. Results In 30 patients undergoing CPB, there is a significant increase in plasma Hb-positive Exos but not microvesicles 30 minutes post-XCR versus other time points, with a simultaneous decrease in the haptoglobin/Hb ratio. These changes presage a significant increase in urine neutrophil gelatinase–associated lipocalin and kidney injury molecule-1 at 24 hours. Intravenous injection of plasma Exos (109-10 particles obtained 30 minutes post-XCR) into rats causes AKI at 72 hours, manifested by multifocal degeneration of proximal tubular epithelium. At 21 days, there is persistent tubular injury and interstitial fibrosis. Intravenous injection of Exos from 35-day-old stored RBCs into rats results in glomerular–tubular injury, increased kidney ferritin and hemoxygenase-1 expression, and significant elevation of kidney injury molecule-1 and proteinuria at 72 hours. Conclusions These combined studies raise the potential for RBC-derived Exos, released during CPB, to target the kidney and mediate AKI.

The development of antibody-drug conjugates composed of a cytotoxic agent and a monoclonal antibody carrier offers an important alternative to classic chemotherapy strategies. Trastuzumab deruxtecan (DS-8201a) is a next-generation antibody-drug conjugate composed of a monoclonal anti-HER2 antibody and a topoisomerase I inhibitor, an exatecan derivative (DX-8951f). DS-8201a resulted in favorable outcomes in HER2-positive heavily pretreated breast cancer patients and also had a promising efficacy in patients with HER2-negative/low-expressing disease, whose options are limited. Interestingly, a recently published phase 2 trial (NCT03248492) reported 60% overall response and 97% disease control in patients with HER2-positive disease previously treated with multiple regimens, including trastuzumab emtansine. On the basis of recent clinical trials, the US Food and Drug Administration granted accelerated approval to DS-8201a in advanced or unresectable HER2-positive breast cancer pretreated with at least two HER2-targeting treatment lines. We review all preclinical and clinical data of DS-8201a regarding breast cancer.

Case An 80 year old man presented with persistent dyspnea two months following placement of three MitraClip devices for severe degenerative mitral regurgitation (MR). On exam, he had an apical holosystolic murmur. A transesophageal echocardiogram revealed displacement of one of the MitraClip devices (Figure 1A, red arrow showing the displaced MitraClip) and moderate-severe MR (Figure 1B). He underwent implantation of a fourth MitraClip with reduction of his MR to mild-moderate (Figure 1C, 1D; yellow arrow showing the new MitraClip). Shortly after, he experienced severe melena and hematochezia and became lethargic and hypotensive. He was transferred to the Cardiac Intensive Care Unit, was intubated and aggressively supported. Extensive work-up revealed diffuse gastric body ischemia and ulceration. A transthoracic echocardiogram showed his most recent MitraClip being well seated with mild-moderate MR. He developed refractory multi-organ failure and expired eight days following the procedure. Autopsy revealed thrombi attached to the initially placed MitraClip’s (Figure 1E, 1F) and thromboemboli to the small bowel, spleen and brain. Discussion MitraClip is the predominant non-surgical alternative for percutaneous mitral valve repair in inoperable patients with symptomatic MR, either primary or secondary. Despite its growing use, there remains a paucity of data on its safety and the potential life-threatening complications, especially when more than one device are placed. Current recommendations include dual antiplatelet therapy with aspirin and clopidogrel. In patients already on anticoagulation, continuation of it is recommended. Very few cases of MitraClip thrombosis have been reported so far. Acute development of spontaneous echo contrast (SEC) and early thrombus was described in a patient with severe, primary MR receiving 2 MitraClip"s. Both SEC and the early thrombus resolved once the second device was removed. In another case, intraprocedural thrombus formation was described on the right side of the interatrial septum close to the MitraClip guide catheter. The underlying pathophysiologic mechanism and the predisposing factors to acute and subacute thrombosis associated with MitraClip are unclear. One plausible explanation could be the acute dramatic hemodynamic alterations related to the reduction in MR and new mild mitral stenosis. In addition, the MitraClip itself may act as a prothrombotic nidus. Potential risk factors include: advanced age and multiple comorbidities predisposing to proinflammation and prothrombosis. The use of MitraClip is only expected to increase in the future. Large scale clinical trials are needed to further define the safety of the device and delineate the optimal antiplatelet and/or antithrombotic regimen. Abstract 496 Figure. Pre and post TEE and autopsy findings.

OBJECTIVE: To characterize symptoms and disease severity among pregnant women with coronavirus disease 2019 (COVID-19) infection, along with laboratory findings, imaging, and clinical outcomes. METHODS: Pregnant women with COVID-19 infection were identified at two affiliated hospitals in New York City from March 13 to April 19, 2020, for this case series study. Women were diagnosed with COVID-19 infection based on either universal testing on admission or testing because of COVID-19-related symptoms. Disease was classified as either 1) asymptomatic or mild or 2) moderate or severe based on dyspnea, tachypnea, or hypoxia. Clinical and demographic risk factors for moderate or severe disease were analyzed and calculated as odds ratios (ORs) with 95% CIs. Laboratory findings and associated symptoms were compared between those with mild or asymptomatic and moderate or severe disease. The clinical courses and associated complications of women hospitalized with moderate and severe disease are described. RESULTS: Of 158 pregnant women with COVID-19 infection, 124 (78%) had mild or asymptomatic disease and 34 (22%) had moderate or severe disease. Of 15 hospitalized women with moderate or severe disease, 10 received respiratory support with supplemental oxygen and one required intubation. Women with moderate or severe disease had a higher likelihood of having an underlying medical comorbidity (50% vs 27%, OR 2.76, 95% CI 1.26-6.02). Asthma was more common among those with moderate or severe disease (24% vs 8%, OR 3.51, 95% CI 1.26-9.75). Women with moderate or severe disease were significantly more likely to have leukopenia and elevated aspartate transaminase and ferritin. Women with moderate or severe disease were at significantly higher risk for cough and chest pain and pressure. Nine women received ICU or step-down-level care, including four for 9 days or longer. Two women underwent preterm delivery because their clinical status deteriorated. CONCLUSION: One in five pregnant women who contracted COVID-19 infection developed moderate or severe disease, including a small proportion with prolonged critical illness who received ICU or step-down-level care.

Patent foramen ovale (PFO) is a residual, oblique, slit or tunnel like communication in the atrial septum that persists into adulthood. It is usually an incidental finding with no clinical repercussions. Nevertheless, recent evidence supports the association between the presence of a PFO and a number of clinical conditions, most notably cryptogenic stroke (CS). There is enough evidence that paradoxical embolism is a mechanism which can explain this association. Patient characteristics and certain echocardiography-derived anatomical and hemodynamic features of PFO provide great assistance in estimating the probability of paradoxical embolism. In this review, we initially describe PFO embryology and anatomy. We extensively present the available data on clinical, anatomical and hemodynamic features of PFOs which have been correlated with increased likelihood of paradoxical embolism and recent evidence of therapeutic management.

A few cases of oral schwannomas in paediatric patients have appeared in the literature so far; however, there are no studies focusing solely on paediatric oral schwannomas. The aim of this study is to report a case of palatal schwannoma in a young female patient and review the pertinent literature on oral schwannomas in paediatric patients. A 12-year-old girl presented with a growing swelling of 2 weeks duration on the hard palate. With a provisional diagnosis of a salivary gland neoplasm an incisional biopsy was performed under local anesthesia and the histologic examination disclosed an Antony A type schwannoma. Complete surgical resection of the lesion was performed under local anaesthesia through a palatal mucosa incision and paraffin gauze was sutured on the surgical area for protection during secondary healing. The bone underlying the tumor was normal. The postoperative period was uneventful and 2 weeks after excision the gauze were removed. There have been no signs of recurrence during a 18-month follow up period. A palatal swelling in a child or adolescent may represent a neoplasm, such as a schwannoma and requires careful clinical and radiographic evaluation of the dentition.

The increasing demand for cosmetic procedures in the orofacial area nowadays, results in a growing number of complications attributable to soft tissue fillers, including the development of foreign body granuloma. The purpose of this study is to present two additional cases of oral foreign body granulomas caused by liquid silicone and hyaluronic acid respectively and review the pertinent literature regarding the demographics, the clinical appearance, the histopathology and the treatment of these lesions. Key words:Oral foreign body granuloma, hyaluronic acid, silicone, soft tissue filler.

BACKGROUND Prematurity is one of the leading causes of perinatal morbidity and mortality. Some studies suggest that respiratory disease may differ by race in early preterm infants. However, the role of race in late preterm neonatal morbidity is not yet established. OBJECTIVE The objective of our study was to determine whether neonatal respiratory morbidity differs by race in neonates born late preterm. STUDY DESIGN This was a secondary analysis of a randomized trial of women at high risk for late preterm delivery (Antenatal Late Preterm Steroids). Our study was limited to women with nonanomalous, singleton gestations, delivering between 34+0 to 36+6 weeks. Women were categorized into 4 groups by race: Black, White, Asian, or other/mixed. The primary outcome was a neonatal composite of treatment in the first 72 hours (continuous positive airway pressure or high-flow nasal cannula >2 hours, oxygen >4 hours, extracorporeal membrane oxygenation or mechanical ventilation) or stillbirth or neonatal death before 72 hours. The secondary outcomes included severe respiratory morbidity (the primary outcome extending continuous positive airway pressure or high-flow nasal cannula to >12 continuous hours and oxygen to at least 24 continuous hours), respiratory distress syndrome, transient tachypnea of the newborn, apnea, neonatal intensive care unit admission, bronchopulmonary dysplasia, and surfactant administration. The primary and secondary outcomes were assessed in the active (steroid) and placebo groups separately. We fit a logistic regression model to adjust for confounders related to respiratory morbidity. RESULTS Of a total of 2331 included women, 26.9% (n=627) were Black/African American, 57.1% (n=1333) White, 3.56% (n=83) Asian, and 12.36% (n=288) were other/mixed. In the placebo group, the rate of the primary outcome was significantly higher in Whites (18.6%) and Asians (22.8%) compared with the African American/Black group (12.3%) (P=.03). Adjusting for confounders, the primary outcome was not significant between the groups. The primary predictor for respiratory morbidity was a prior pregnancy with neonatal respiratory morbidity. Findings were similar in the steroid group, but severe respiratory morbidity was less common in Black infants compared with White infants (adjusted odds ratio, 0.45; 95% confidence interval, 0.24–0.83). However, a prior pregnancy with neonatal respiratory complications was no longer associated with respiratory morbidity after receipt of betamethasone. CONCLUSION Late preterm respiratory morbidity was similar between racial groups. Although a history of pregnancy with previous neonatal respiratory disease is the strongest risk factor for recurrence, this risk factor is mitigated by the receipt of steroids.

Simple Summary MicroRNAs are endogenous non-coding 20–22 nucleotide long RNAs that play a fundamental role in the post-transcriptional control of gene expression. Consequently, microRNAs are involved in multiple biological processes of cancer and could be used as biomarkers with prognostic and predictive significance. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have become a mainstay of treatment for patients with advanced hormone receptor-positive (HR) breast cancer. Despite the initial high response rates, approximately 10% of patients demonstrate primary resistance to CDK4/6 inhibitors while acquired resistance is almost inevitable. Considering the fundamental role of miRNAs in tumorigenesis, we aimed to explore the potential involvement of microRNAs in response to CDK4/6 inhibition in solid tumors. A number of microRNAs were shown to confer resistance or sensitivity to CDK4/6 inhibitors in preclinical studies, although this remains to be proved in human studies. Abstract Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have emerged as novel treatment options in the management of advanced or metastatic breast cancer. MicroRNAs are endogenous non-coding 19–22-nucleotide-long RNAs that regulate gene expression in development and tumorigenesis. Herein, we systematically review all microRNAs associated with response to CDK4/6 inhibitors in solid tumors and hematological malignancies. Eligible articles were identified by a search of the MEDLINE and ClinicalTrials.gov databases for the period up to1 January 2021; the algorithm consisted of a predefined combination of the words “microRNAs”, “cancer” and “CDK 4/6 inhibitors”. Overall, 15 studies were retrieved. Six microRNAs (miR-126, miR-326, miR3613-3p, miR-29b-3p, miR-497 and miR-17-92) were associated with sensitivity to CDK4/6 inhibitors. Conversely, six microRNAs (miR-193b, miR-432-5p, miR-200a, miR-223, Let-7a and miR-21) conferred resistance to treatment with CDK4/6 inhibitors. An additional number of microRNAs (miR-124a, miR9, miR200b and miR-106b) were shown to mediate cellular response to CDK4/6 inhibitors without affecting sensitivity to treatment. Collectively, our review provides evidence that microRNAs could serve as predictive biomarkers for treatment with CDK4/6 inhibitors. Moreover, microRNA-targeted therapy could potentially maximize sensitivity to CDK4/6 inhibition.

Background: Aromatase inhibitors (AIs) are associated with musculoskeletal pain in one third (20–47%) of breast cancer patients. Recently, CDK4/6 inhibitors have emerged as a new therapeutic approach in hormone receptor (HR)-positive breast cancer. While hematological and gastrointestinal toxicities are frequently reported during treatment with CDK4/6 inhibitors, musculoskeletal symptoms are less commonly encountered. Methods: Herein, we present a retrospective study of 47 breast cancer patients who received CDK4/6 inhibitors along with endocrine therapy in our department between 01/01/2018 and 01/09/2020. Results: Median age at diagnosis was 58 years (29–81). Median duration of treatment was 8.76 months (SD: 7.68, 0.47–30.13 months). Median PFS was 24.33 months (95% CI, 1.71–46.96). Overall, toxicity was reported in 61.7% of the cases (29/47). Arthralgia was reported in 6.4% (3/47) of the patients. Hematological toxicity was reported in 51.1% (24/47) of the patients. Neutropenia was the main hematological toxicity observed (86.8%, 22/47) along with anemia (4.3%, 2/47), thrombocytopenia (2.1%, 1/47), and leukopenia (4.2%, 1/24). Conclusions: Though our data reflect a small sample size, we report a reduced arthralgia rate (6.4%) during treatment with CDK4/6 inhibitors compared with that reported in studies of AIs (20–47%).

Objective To characterize risk and temporal trends for preeclampsia and related outcomes by maternal age. Study Design Deliveries to women aged 15 to 54 years in the 1998 to 2014 National Inpatient Sample who had a diagnosis of preeclampsia, eclampsia, or both were included in the analysis. Age was categorized as 15 to 17, 18 to 24, 25 to 29, 30 to 34, 35 to 39, 40 to 44, and 45 to 54 years. The primary outcome was temporal trends in preeclampsia based on maternal age. Secondary outcomes analyzed included risk for severe maternal morbidity. Results The proportion of women with preeclampsia aged 15 to 24 years decreased from 42.3% in 1998 to 30.1% in 2014, while preeclampsia among those 30 to 54 years increased from 32.9 to 43.7%. Preeclampsia risk increased for all groups over the study period. Risk for severe morbidity by age group with and without transfusion was “U-shaped,” with risk highest for women 18 to 24 and 40 to 54 years. The risk for abruption, acute renal failure, acute heart failure or pulmonary edema, and stroke was lowest for women aged 15 to 24 years and increased in a “dose-dependent” manner with increasing maternal age. In contrast, eclampsia risk was highest for women aged 15 to 17 years. Conclusion With a changing demographic profile of preeclampsia, older women accounted for an increasing proportion of preeclampsia and related adverse outcomes.

Dementia is estimated to affect 50 million people worldwide [1]. A significant proportion of residents in residential homes are people with moderate to severe dementia [2, 3]. Apathy amongst them is a major issue [3, 4, 5]. Tovertafel is an interactive table that was designed to reduce apathy and to facilitate play for people with moderate to severe dementia [6].